POS0323 RISK FACTORS FOR MAJOR CARDIOVASCULAR EVENTS (MACE) IN INFLAMMATORY ARTHRITIS: A TIME-DEPENDENT ANALYSIS ON INFLAMMATORY BURDEN, USE OF NSAIDs, STEROID AND DMARDs
Authors: H. Meng, S. H. M. Lam, H. So, L. S. Tam
Journal: Annals of the Rheumatic Diseases (2022)

Background Inflammatory arthritis (IA) including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylarthritis (AS) are associated with accelerated atherosclerosis due to systematic inflammation. Objectives To elucidate whether inflammatory burden (c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR] levels) and drugs used to suppress inflammation (disease modifying anti-rheumatic drugs [DMARDs] and non-steroidal anti-inflammatory drugs [NSAIDs]) over time are independently associated with major cardiovascular events (MACE) in patients with IA. Methods A population-based cohort of IA patients were identified in the citywide Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority. IA patients recruited from 2006 to 2016 were followed until the end of 2018. The outcome was occurrence of a first MACE, defined as unstable angina, acute myocardial infarction, stroke/transient ischemic attack or death from cardiovascular causes. Cox proportional hazard models with time-varying CRP and ESR levels and drugs used were analyzed to identify the risk of having MACE in IA patients. Results A total of 17,732 (12050 RA patients, 1789 PsA patients and 3893 AS patients) patients with IA were recruited. After a mean follow-up of 8.7 ± 3.1 years, 1,069 (6.0 %) patients developed a first MACE. At baseline, the MACE group were older (68±12 vs 53±15, p &lt;0.001), had more traditional cardiovascular risk factors, higher levels of CRP (2.7±1.5 vs 1.7±1.3, p &lt;0.001) and ESR (57.8±32.4 vs 42.5±29.2, p &lt;0.001), and less exposure to biologic DMARDs (bDMARDs) (1.0% vs 3.0%, p &lt;0.001) and non-selective NSAIDs (nsNSAIDs) (63.4% vs 71.1%, p &lt;0.001). After adjusting for age, sex, baseline cardiovascular comorbidities using multivariable Cox regression analysis, IA patients with higher inflammatory burden (as reflected by the time-varying CRP [hazard ratio {HR} 1.11, 95% confidence interval {CI} 1.10-1.12, p &lt;0.001] and ESR levels (HR 1.02, 95% CI 1.01-1.01, p &lt;0.001) and the use of steroid (HR 1.79-1.88) were independently associated with a higher risk of developing MACE (Table 1). In contrast, exposure to nsNSAIDs had a protective effect against MACE (HR 0.76, 95% CI 0.66-0.89, p &lt;0.001), while bDMARDs were not associated with MACE. Table 1. Multivariable time-varying Cox regression models for the predictors of incidence of MACE in the IA patients (n=17732) Model 1 † Model 2 ‡ Variables HR (95% CI) p value HR (95% CI) p value Male 1.92 (1.65-2.23) &lt;0.001* 1.52 (1.33-1.76) &lt;0.001* Age 1.06 (1.05-1.06) &lt;0.001* 1.06 (1.05-1.06) &lt;0.001* Disease duration 1.04 (0.97-1.08) 0.056 1.04 (1.01-1.08) 0.016* Baseline DM 1.25 (0.95-1.64) 0.108 1.44 (1.13-1.84) 0.003* Baseline HT 1.77 (1.52-2.08) &lt;0.001* 1.85 (1.59-2.16) &lt;0.001* Baseline LP 1.14 (0.92-1.41) 0.232 1.19 (0.98-1.46) 0.081 Time-varying inflammatory markers ESR 1.02 (1.01-1.01) &lt;0.001* CRP 1.11 (1.10-1.12) &lt;0.001* Time-varying treatment bDMARDs 0.93 (0.68-1.27) 0.657 0.89 (0.65-1.22) 0.478 CoxII 0.71 (0.53-0.96) 0.027* 0.79 (0.59-1.04) 0.104 nsNSAIDs 0.76 (0.66-0.89) &lt;0.001* 0.76 (0.66-0.88) &lt;0.001* Steroids 1.88 (1.63-2.17) &lt;0.001* 1.79(1.56-2.04) &lt;0.001* *Statistically significant at p &lt; 0.05. † and ‡ Adjusted for Age, Sex, Hypertension at baseline, diabetes mellitus at baseline, dyslipidemia at baseline, bDMARDs, CoxII, non-selective NSAIDs, Steroids. CRP, C-reactive protein; ESR: Erythrocyte sedimentation rate; HT: hypertension; DM: diabetes mellitus; LP: Dyslipidemia; bDMARD, biological disease-modifying anti-rheumatic drug; COXII: cyclooxygenase -2 inhibitors; nsNSAIDs: non-selective nonsteroidal anti-inflammatory drugs. Conclusion Increased inflammatory burden as reflected by elevated ESR and CRP level over time, and increased exposure to steroid were independently associated with increased risk of MACE, while the risk was significantly reduced with non-selective NSAIDs use in IA patients. Disclosure of Interests None declared